International Study of Subsequent Colorectal Cancer Among Survivors of Childhood, Adolescent, and Young Adult Cancers (I-SCRY)

项目总结/摘要 儿童、青少年和年轻成人（AYA）癌症的幸存者， 与发病率和过早死亡率相关的恶性肿瘤。新出现的证据 提示结直肠癌（CRC），与腹部或盆腔放疗用于治疗 儿童癌症或AYA癌症就是这样一种肿瘤。早期的研究表明，其他治疗暴露，包括 顺铂和烷化剂治疗也可能与CRC风险相关，并可能与放疗相互作用， 会带来明显的高风险关于暴露于这些治疗的年龄是否可能改变风险的知识是 有限公司此外，治疗相关CRC后的预后尚不清楚。这些知识差距是 由于任何单一队列中CRC数量有限，缺乏原发性癌症的详细信息 一些队列的治疗，队列相对年轻的年龄，以及现有队列的重点是 儿童癌症幸存者或特定的年轻成人癌症幸存者。 我们建议利用八个国际儿童和AYA癌症幸存者的独特资源， 同伙我们将汇总51，309名幸存者的个体参与者数据，其中298名患有CRC，并进行中位随访 在原发性癌症诊断后13至26年的研究中， 随后的CRC的因素和死亡率。这几乎是任何已知国家CRC数量的四倍。 有详细治疗数据的儿童或AYA队列。因此，童年和AYA的结合 将癌症幸存者纳入单一队列是新颖的，并给予儿科和AYA常见的治疗方法。 癌症，将使我们能够解决这些问题的能力，以评估年龄在暴露的作用。 该项目的主要目的是评估儿童和AYA癌症治疗的相关性 （腹部和/或盆腔辐射野和剂量，以及化疗暴露，包括累积 剂量的烷化剂、蒽环类、铂类药物）对CRC风险的影响。 幸存人口。次要目标将侧重于对CRC负担进行扩大评估 在儿童和癌症幸存者中。这包括估计和比较结直肠癌的发病率， 儿童和AYA癌症幸存者与一般人群中CRC发病率的关系，以及 描述儿童和AYA癌症幸存者中CRC诊断后的死亡率，并将其与 这是在一般人群中新发CRC诊断后观察到的。 这项工作的结果有可能帮助完善筛查指南和策略， 预防CRC。此外，为了实现我们的目标，我们将建立一种资源， 未来的研究方向。

PROJECT SUMMARY / ABSTRACT Survivors of childhood, adolescent, and young adult (AYA) cancer have an elevated risk of subsequent malignant neoplasms which are associated with morbidity and premature mortality. Emerging evidence suggests that colorectal cancer (CRC), associated with abdominal or pelvic radiotherapy used to treat the childhood or AYA cancer, is one such neoplasm. Early studies indicate other treatment exposures, including cisplatin and alkylator therapy, may also be associated with CRC risk and may interact with the radiotherapy to confer a markedly elevated risk. Knowledge of whether age at exposure to these therapies might modify risk is limited. Further, prognosis after a treatment-related CRC is not well-understood. These gaps in knowledge are due to the limited number of CRCs in any single cohort, lack of detailed information on primary cancer treatments for some cohorts, the relatively young age of cohorts, and the focus of existing cohorts on either childhood cancer survivors or on survivors of specific young adult cancers. We propose to leverage the unique resources of eight international childhood and AYA cancer survivor cohorts. We will pool individual participant data on 51,309 survivors, 298 with CRC, and with median follow-up across studies ranging from 13 to 26 years after primary cancer diagnosis, to comprehensively examine risk factors of, and mortality after, subsequent CRCs. This is almost four-fold the number of CRCs in any known childhood or AYA cohort with detailed treatment data available. Thus, the combination of childhood and AYA cancer survivors into a single cohort is novel and given common treatment approaches to pediatric and AYA cancer, will enable us to address these questions with the ability to assess the role of age at exposure. The primary aim of this project is to evaluate the association of childhood and AYA cancer therapy (abdominal and/or pelvic radiation fields and dose, as well as chemotherapy exposures including cumulative doses of alkylating agents, anthracyclines, platinating agents) on CRC risk in a large, multi-cohort, international survivor population. Secondary aims will focus on conducting an expanded assessment of the burden of CRC in childhood and AYA cancer survivors. This includes estimating and comparing the incidence of CRC in childhood and AYA cancer survivors to the incidence of CRC in the general population, as well as characterizing mortality following a CRC diagnosis in childhood and AYA cancer survivors and comparing it to that observed following a de novo CRC diagnosis in the general population. The results from this work have the potential to help refine screening guidelines and strategies for preventing CRC. In addition, in achieving our aims, we will establish a resource that may be leveraged for future investigator-initiated research.